Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients.

Détails

ID Serval
serval:BIB_57F07E73D442
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients.
Périodique
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Auteur⸱e⸱s
Lavoie S., Murray M.M., Deppen P., Knyazeva M.G., Berk M., Boulat O., Bovet P., Bush A.I., Conus P., Copolov D., Fornari E., Meuli R., Solida A., Vianin P., Cuénod M., Buclin T., Do K.Q.
ISSN
0893-133X
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
33
Numéro
9
Pages
2187-99
Langue
anglais
Notes
Publication types: Clinical Trial ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
In schizophrenia patients, glutathione dysregulation at the gene, protein and functional levels, leads to N-methyl-D-aspartate (NMDA) receptor hypofunction. These patients also exhibit deficits in auditory sensory processing that manifests as impaired mismatch negativity (MMN), which is an auditory evoked potential (AEP) component related to NMDA receptor function. N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients to determine whether increased levels of brain glutathione would improve MMN and by extension NMDA function. A randomized, double-blind, cross-over protocol was conducted, entailing the administration of NAC (2 g/day) for 60 days and then placebo for another 60 days (or vice versa). 128-channel AEPs were recorded during a frequency oddball discrimination task at protocol onset, at the point of cross-over, and at the end of the study. At the onset of the protocol, the MMN of patients was significantly impaired compared to sex- and age- matched healthy controls (p=0.003), without any evidence of concomitant P300 component deficits. Treatment with NAC significantly improved MMN generation compared with placebo (p=0.025) without any measurable effects on the P300 component. MMN improvement was observed in the absence of robust changes in assessments of clinical severity, though the latter was observed in a larger and more prolonged clinical study. This pattern suggests that MMN enhancement may precede changes to indices of clinical severity, highlighting the possible utility AEPs as a biomarker of treatment efficacy. The improvement of this functional marker may indicate an important pathway towards new therapeutic strategies that target glutathione dysregulation in schizophrenia.
Mots-clé
Acetylcysteine, Acoustic Stimulation, Adult, Brain Mapping, Cerebral Cortex, Contingent Negative Variation, Cross-Over Studies, Discrimination (Psychology), Double-Blind Method, Electroencephalography, Evoked Potentials, Auditory, Female, Free Radical Scavengers, Glutathione, Humans, Male, Middle Aged, Neuropsychological Tests, Reaction Time, Retrospective Studies, Schizophrenia, Time Factors
Pubmed
Web of science
Open Access
Oui
Création de la notice
19/02/2009 16:13
Dernière modification de la notice
20/08/2019 14:11
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